These studies seek to assess the effects of environmental agents on spermatogenesis. Enviromental chemicals are tested, test systems validated and new approaches to toxicity testing proposed: (1) examine germ cell repair and DNA synthesis as indicators for chemical mutagenesis; (2) utilize an integrated approach to study toxic effects on reproductive function; and (3) investigate the toxication-detoxication of polycyclic hydrocarbons in gonadal tissue. To date, selected mutagens, trace metals and Freon 22 have been studied. A new sensitive alkaline elution analysis of germ cell DNA appears to be useful as a predictor of environmental agents which damage DNA. A DNA repair deficient mouse strain has been sought. Biochemical and toxic effects of environmental agents on rodent spermatogenesis are also studied by an integrated approach using spermatogenic "marker" enzymes, plasma FSH, LH, testosterone, histologic changes, and the in vitro perfusion of testis with selected environmental chemicals. These biochemical and toxic effects were correlated to functionality of spermatozoa through serial mating studies. These studies contribute to an improved understanding of mechanism of toxicity, the reliability of laboratory animal toxicity tests for mutagenic and reproductive effects and validity of their extrapolation to humans. BIBLIOGRAPHIC REFERENCES: Shen, R. S. and Lee, I. P.: Developmental Patterns of Enzymes in Mouse Testis. J. Reproduction and Fertility 48: 301-305, 1976. Lee, I. P., Schmid, B., and Zbinden, G.: A Simplified Method for the Isolation of Sperm Heads from the Caput Epididymidis of Rodents and from Ejaculated Rabbit Seminal Plasma. Exper. Cell Biology 45: 48-59, 1977.